Beta-Site APP-Cleaving Enzyme-1 Inhibitory Role of Natural Flavonoids in the Treatment of Alzheimer's Disease.
Cent Nerv Syst Agents Med Chem
; 2024 Jul 12.
Article
in En
| MEDLINE
| ID: mdl-39005132
ABSTRACT
Alzheimer's Disease (AD) is a devastating neurological condition characterized by a progressive decline in cognitive function, including memory loss, reasoning difficulties, and disorientation. Its hallmark features include the formation of neurofibrillary tangles and neuritic plaques in the brain, disrupting normal neuronal function. Neurofibrillary tangles, composed of phosphorylated tau protein and neuritic plaques, containing amyloid-ß protein (Aß) aggregates, contribute to the degenerative process. The discovery of the beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) in 1999 revolutionized our understanding of AD pathogenesis. BACE1 plays a crucial role in the production of Aß, the toxic protein implicated in AD progression. Elevated levels of BACE1 have been observed in AD brains and bodily fluids, underscoring its significance in disease onset and progression. Despite setbacks in clinical trials of BACE1 inhibitors due to efficacy and safety concerns, targeting BACE1 remains a promising therapeutic strategy for early-stage AD. Natural flavonoids have emerged as potential BACE1 inhibitors, demonstrating the ability to reduce Aß production in neuronal cells and inhibit BACE1 activity. In our review, we delve into the pathophysiology of AD, highlighting the central role of BACE1 in Aß production and disease progression. We explore the therapeutic potential of BACE1 inhibitors, including natural flavonoids, in controlling AD symptoms. Additionally, we provide insights into ongoing clinical trials and available patents in this field, shedding light on future directions for AD treatment research.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Cent Nerv Syst Agents Med Chem
Journal subject:
FARMACOLOGIA
/
NEUROLOGIA
/
QUIMICA CLINICA
Year:
2024
Document type:
Article